Sharma Gajanand, Dhankar Geeta, Thakur Kanika, Raza Kaisar, Katare O P
Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh, 160 014, India.
Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Dist., Ajmer, Rajasthan, 305 817, India.
AAPS PharmSciTech. 2016 Oct;17(5):1221-31. doi: 10.1208/s12249-015-0464-0. Epub 2015 Dec 15.
Benzyl benzoate (BB) is one of the oldest drugs used for the treatment of scabies and is recommended as the "first-line intervention" for the cost-effective treatment of the disease. Though a promising candidate, its application is reported to be associated with irritation of the skin and eye, resulting in poor patient compliance. Hence, the present study aims to develop BB-loaded topical microemulsion for the safer and effective delivery of BB. Pseudo-ternary phase diagrams with BB as the oily phase itself, along with Tween 80 as surfactant, and mixture of phospholipid and ethanol as the co-surfactant along with aqueous solution as the external phase were constructed and various compositions were formulated. The optimized formulation was characterized for particle-size, zeta-potential, drug-content, globule-morphology pH, and refractive-index, whereas evaluated for skin permeation, retention, compliance, and dermatokinetics. The nanosized formulation offered threefold higher drug permeation vis-a-vis plain drug solution across LACA mice abdominal skin. The drug retention of the selected formulation was nearly twice of that from the marketed product, assuring depot formulation and sustained release. The skin histopathology revealed the non-irritant nature of the formulation, as no changes in the normal skin histology were observed. The dermatokinetic studies confirmed better permeation and enhanced skin bioavailability of BB to epidermis as well as dermis vis-à-vis the conventional product. The results indicate that the developed lipid-based microemulsion hydrogel can alleviate the concerns associated with BB and can provide a better and safer delivery option in substantial amounts to various skin layers.
苯甲酸苄酯(BB)是用于治疗疥疮的最古老药物之一,被推荐作为该疾病经济有效治疗的“一线干预措施”。尽管它是一个有前景的候选药物,但据报道其应用与皮肤和眼睛刺激有关,导致患者依从性差。因此,本研究旨在开发负载BB的局部微乳剂,以更安全有效地递送BB。构建了以BB本身为油相、吐温80为表面活性剂、磷脂和乙醇混合物为助表面活性剂以及水溶液为外相的伪三元相图,并配制了各种组合物。对优化后的制剂进行了粒径、zeta电位、药物含量、球粒形态、pH值和折射率的表征,同时评估了其皮肤渗透、滞留、依从性和皮肤动力学。与普通药物溶液相比,纳米制剂在LACA小鼠腹部皮肤的药物渗透率提高了三倍。所选制剂的药物滞留率几乎是市售产品的两倍,确保了长效制剂和缓释效果。皮肤组织病理学显示该制剂无刺激性,因为未观察到正常皮肤组织学的变化。皮肤动力学研究证实,与传统产品相比,BB在表皮和真皮中的渗透更好,皮肤生物利用度更高。结果表明,所开发的脂质基微乳水凝胶可以缓解与BB相关的问题,并能以大量向不同皮肤层提供更好、更安全的递送选择。